tbuckley/cabot-search huggingface dataset:
Abstract 10138: Exercise Inhibits Doxorubicin-Induced Cardiotoxicity by Preventing Cardiomyocyte Cellular Senescence
Authors: Prince Jeyabal, Zhanglong Peng, eugenie kleinerman
Journal: Circulation (2022)

Introduction: Doxorubicin (Dox) induces cardiomyocyte cellular senescence thru proinflammatory mechanisms and by damaging DNA, resulting in Dox-induced cardiotoxicity. Inhibiting cardiomyocyte cellular senescence inhibits Dox-induced cardiac damage. We showed that exercise inhibits both acute and late Dox-induced cardiotoxicity using our juvenile cardiotoxicity mouse model. Here we used p16-3MR transgenic mice to track the induction of senescent cardiomyocytes to determine whether exercise prevents Dox-induced cardiotoxicity by inhibiting senescence. Hypothesis: Cellular senescence plays a key role in Dox-induced cardiotoxicity in the heart following therapy. Exercise prevents Dox-induced cardiotoxicity by inhibiting myocardial cell senescence. Methods: To confirm induction of senescence by Dox in vitro , mouse cardiomyocytes were isolated and treated with 250 nmol/L Dox for 24 h for 24h cells, washed and then analyzed 7 days later for senescent markers. Mice were treated with PBS, Dox (2.5mg/kg 2x/wk for 2 wks), or Dox + exercise (walking 45 min/day at 12 meter/min). Cardiac function was evaluated by echocardiography 24 h after therapy to confirm Dox-induced cardiotoxicity. Heart tissue was collected 14 days after therapy. Tissue sections were analyzed by immunohistochemical and Western immunoblot. Results: Dox-induced senescence was confirmed by a significant increase in β-galactosidase in cardiomyocytes from the in vitro study. Decreased ejection fraction, fractional shortening and F-actin distribution was seen in Dox but not Dox + exercise-treated mice confirming Dox-induced cardiotoxicity and prevention of heart damage by exercise. There was an increase in p16 INK4a expression (signifying senescent cells) in cardiac tissue from Dox-treated but not Dox + exercise-treated mice compared with PBS controls. Conclusion: Taken together our data demonstrated that exercise inhibited Dox-induced cardiotoxicity by inhibiting the induction of cardiomyocyte senescence.
Abstract 10409: Performance of the Hart Cve Panel for Prediction of Cardiovascular Events in Patients With Chronic Kidney Disease
Authors: Reza Mohebi, Cian McCarthy, Roland van Kimmenade, Hanna K Gaggin, Rhonda F Rhyne, Craig Magaret, Grady Barnes, James L Januzzi
Journal: Circulation (2022)

Background: Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular events (CVE: incident myocardial infarction [MI], stroke, or cardiovascular death) following an angiographic procedure. Methods: Among 446 patients undergoing coronary or peripheral angiography, we applied a previously-developed biomarker panel to predict incident cardiovascular events (HART CVE, Prevencio, Kirkland WA); the panel consists of 4 biomarkers (N-terminal pro-B type natriuretic peptide, kidney injury molecule-1, osteopontin, and tissue inhibitor of matrix metalloproteinase-1) with results expressed in 2 risk levels (CVE high risk and low risk). Patients were followed for 2 years for incident cardiovascular events. Results: During the 2-year follow-up, 74 CVE occurred. Participants were categorized into four groups based on CKD stages (Stage 1-2 vs Stage 3-5) and CVE risk level (high risk and low risk). In our multivariable model, considering patients at CKD stage 1-2/CVE low-risk as a reference, the hazard ratio (95 % confidence interval) of cardiovascular events was 2.28 (1.53-5.22) for CKD stage 1-2/CVE high-risk, 0.50 (0.07-3.73) for CKD stage 3-5/CVE low-risk and 4.56 (2.54-8.18) for CKD stage 3-5/CVE high-risk ( Table ). The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82). Conclusion: Patients with CKD are at high risk for incident MI, stroke, and CV death. Utilizing a multiple-protein biomarker panel can assist clinicians in identifying patients at higher risk of CVE, particularly among those at high stages of CKD.
Abstract 10553: Staged Percutaneous Coronary Intervention For Chronic Total Occlusion of Non-Infarct Related Artery: A Meta-Analysis
Authors: Noman Lateef, Muhammad J Ahsan, Soban Ahmad, Muhammad Atif Masood Noori, Azka Latif, Kristen Brown, Andrew M Goldsweig
Journal: Circulation (2022)

Background: Chronic total occlusion (CTO) of a non-infarct related artery (nIRA) is associated with adverse outcomes following acute myocardial infarction (AMI). The current study aimed to evaluate the impact of successful staged percutaneous coronary intervention (PCI) of nIRA CTO lesions on clinical outcomes. Methods: PubMed, EMBASE, Google Scholar and Scopus databases were queried for studies comparing outcomes between AMI patients who underwent successful staged PCI of nIRA CTO lesions (CTO PCI group) and AMI patients with medical management of nIRA CTO lesions or failed CTO PCI attempt (No CTO PCI group). The primary meta-analysis outcome was major adverse cardiovascular events (MACE). The main summary estimate was the random effects risk ratio (RR) with 95% confidence intervals (CIs). Results: Eleven studies (1 randomized, 10 observational) with 2,788 patients were included. Compared with the No CTO PCI group, the CTO PCI group demonstrated a lower incidence of MACE (Figure A, RR 0.55 [0.46, 0.66], p&lt;0.001), all-cause mortality (Figure B, RR 0.47 [0.33, 0.66], p&lt;0.001), cardiac mortality (Figure C, RR 0.4 [0.28, 0.59], p&lt;0.001), stroke (Figure D, RR 0.38 [0.22, 0.66], p=0.0007) and heart failure (HF) hospitalization (RR 0.61 [0.41, 0.9], p=0.01). There was no significant difference in rates of any repeat revascularization (Figure E, RR 0.98 [0.69, 1.4], p=0.92) or target vessel revascularization (Figure F, RR 0.81 [0.48, 1.37], p=0.43) between the two groups. Conclusion In patients with AMI, staged PCI of nIRA CTO lesions was associated with a significantly lower incidence of MACE, all-cause mortality, cardiac mortality, stroke and HF hospitalization.
Abstract 02: Intravenous Oxygen Microparticles as Resuscitative Fluid Improves Outcomes in a Swine Model of Asphyxial Cardiac Arrest
Authors: Julia Garcia Mancebo, Kristen Sack, Jay Hartford, Saffron Dominguez, Arthur Nedder, Michelle Barcarcel-Monzon, John Kheir, Yifeng Peng
Journal: Circulation (2022)

Introduction: Asphyxia-induced cardiac arrest (ACA) can lead to organ damage and death within minutes, with a reported survival rate of 25-38%. It is the leading cause of in-hospital cardiac arrest in children and elderly and the second in adults. The direct injection of oxygen as a rescue therapy for ACA is not yet possible. Methods: We manufactured immediate-release intravenous oxygen (IVO 2 ) microparticles with a shell composed of biocompatible dextran polymers formed by nanoprecipitation. Following intravenous injection, the hydrophobic shell transitions from a crystalline state to a rapidly dissolving, fluid shell based on pH (A). IVO 2 was manufactured following Good Manufacturing Practice control over particle size, chemical purity, and sterility. Following instrumentation, Yorkshire swine (n=10 control, n=6 IVO 2 ) underwent complete asphyxia by endotracheal tube occlusion for 12 minutes (B). ACLS was performed whenever SBP&lt;40 mmHg. At minute 6, 8 and 10 of asphyxia, IVO 2 or placebo (20 mL/kg fluid phase) was administered. Animals were then survived for 4 days in an ICU environment, followed by brain MRI and neurohistology. Results: Animals receiving IVO 2 exhibited increased arterial oxygen saturation during asphyxia (p&lt;0.05, C), with less CPR time (p&lt;0.001, D) and higher ROSC (p=0.011, E). Three out of 6 IVO 2 animals vs 0/3 surviving controls were successfully extubated (p=0.035). IVO 2 treatment was associated with increased survival (p=0.037, F) with improved swine neurologic deficit scores (p&lt;0.05, G). MRI (H) and pathology (I) demonstrated devastating hypoxic-ischemic injury in all surviving controls, endpoints that were significantly improved with IVO 2 . No significant adverse effects were noted in hematologic, coagulation, hepatic, or renal function due to IVO 2 . Conclusion: Treatment of ACA with IVO 2 may diminish critical oxygen deficit, resulting in improved survival and neurological outcomes.
Abstract 10373: Associations of Triglyceride-Glucose Index and Morning Home Blood Pressure With Microalbuminuria and Chronic Kidney Disease in the Japanese at High-Risk of Cardiovascular Disease
Authors: Michiaki Nagai, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2022)

Introduction: Triglyceride-glucose index (TyGi) was shown to serve as a simple surrogate marker of insulin resistance, which had a significant association with impaired renal function. However, the underlying pathophysiology has not been established between insulin resistance and impaired renal function in relation to home blood pressure (BP) measurement. Hypothesis: We hypothesized that morning home BP level and TyGi were associated with impaired renal function in the Japanese at high-risk of cardiovascular disease. In addition, an interaction of morning home systolic BP (MSBP) with TyGi was assessed for impaired renal function. Methods: In the Japan Morning Surge-Home Blood Pressure Study, measurements of home BP (mean 11.2 days) were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). TyGi was calculated as ln[fasting triglycerides (mg/dL) х fasting glucose (mg/dL)/2]. While microalbuminuria was defined as urinary albumin/creatinine ratio ≥30 mg/gCr, chronic kidney disease (CKD) was defined as estimated glomerular filtration rate &lt;60 ml/min/1.73 m 2 . Results: The mean levels of MSBP and TyGi were 138±16mmHg and 8.65±0.59, respectively. While the prevalence of microalbuminuria was 25.4%, the prevalence of CKD was 22.7%. In the logistic regression analysis adjusted for confounders including age, gender, body mass index, smoking, total cholesterol, HbA1c, use of antihypertensives, use of antidiabetics, statin use, and office SBP, MSBP (OR per 1SD, 1.39, 95%CI, 1.28-1.50, p&lt;0.001) and TyGi (OR per 1Unit, 1.31, 95%CI, 1.14-1.51, p&lt;0.001) were significantly associated with microalbuminuria. MSBP (OR per 1SD, 1.13, 95%CI, 1.04-1.23, p&lt;0.01) and TyGi (OR per 1Unit, 1.38, 95%CI, 1.19-1.61, p&lt;0.001) were also significantly associated with CKD. A significant interaction of MSBP with TyGi was not observed for microalbuminuria (p=0.17) or CKD (p=0.91). Conclusions: MSBP as well as TyGi were significant indicators of microalbuminuria and CKD. Morning BP load and insulin resistance were additively associated with impaired renal function in the high-risk Japanese population. In addition to home BP measurements, TyGi might provide additional clinically relevant information for target renal damage.
Abstract 103: Regulation Of Cardiac PTEN/Akt Signaling By Moderate Intra-Ischemic Therapeutic Hypothermia
Authors: Cody N Justice, Xiangdong Zhu, Jing Li, J M Odonnell, Terry L Vanden Hoek
Journal: Circulation (2022)

Introduction: Previous studies demonstrate a critical role for Akt in mediating cardioprotection by therapeutic hypothermia. However, the mechanism of hypothermia-induced Akt activation remains poorly understood. Akt activation is determined in part by PTEN activity and degradation. Hypothesis: We hypothesized that moderate intra-ischemic cooling activates Akt in the ischemic-reperfused heart due to enhanced PTEN degradation. Methods: Rat hearts were isolated and perfused media containing 5 mM glucose. LV function was monitored continuously by an intraventricular balloon. Rate-pressure product (RPP=heart rate x LV developed pressure) was monitored as an index of cardiac function. Hearts in the normothermic control group (I/R) were subjected to 20 min. of global, no-flow ischemia followed by reperfusion at 37 °C. In the hypothermia intervention group (I/R+TH), hearts were cooled to 30 °C at the start of ischemia and then rewarmed 10 min. after reperfusion. Coronary perfusate was collected from the pulmonary artery at preischemic baseline and 10 min. after reperfusion. Ventricular tissue was harvested at 0 or 30 min. after reperfusion for western blotting. Results: RPP was significantly higher in the I/R+TH group (n=7) compared to the I/R group (n=8) at 30 min. post-reperfusion (24,725 ± 1,112 mmHg*beats/min. vs. 18,237 ± 2,223 mmHg*beats/min., p&lt;0.05). Coronary perfusate taurine concentration was significantly higher in the I/R group compared to the I/R+TH group at 10 min. post-reperfusion (19 ± 4 μM vs. 5 ± 1 μM, p&lt;0.01). Akt serine473 phosphorylation was significantly higher in the I/R+TH group compared to the I/R group at 0 min. post-reperfusion (p&lt;0.01), but significantly lower at 30 min. post-reperfusion (p&lt;0.01). Additionally, TH enhanced total PTEN expression at 0 min. (p&lt;0.05) and 30 min. (p&lt;0.01) post-reperfusion without affecting the ratio of phospho-PTEN/PTEN. Conclusion: Intra-ischemic cooling was associated with temporal changes in Akt phosphorylation despite enhanced PTEN expression. Additionally, modulation of cardiac taurine release by hypothermia should be carefully considered in future studies assessing taurine as a biomarker for cardiac arrest and ischemic heart pathologies.
Abstract 10311: Atrioventricular Junctional Ablation in Patients With Atrial Fibrillation With and Without Heart Failure: A Meta-Analysis
Authors: Christian Lewinter, Eslem Sögütlü, Torsten Holm H Nielsen, John G Cleland, Lars Kober, Martin M Lewinter, cecilia M Linde, Frieder Braunschweig
Journal: Circulation (2022)

Introduction: Rapid atrial fibrillation (AF) leads to heart failure (HF), but can also result from cardiac remodelling during HF. Atrioventricular junctional ablation (AVJA) cures rapid AF at the cost of permanent pacemaker dependency. We compared mortality in AF patients treated with AVJA to pharmacological therapy. Methods: We performed data searches in the PubMed, Central, and Embase till Marts 31, 2022. Inclusion criteria were observational and randomised controlled trials evaluating mortality and left ventricular ejection fraction (LVEF) in patients with AF. An exclusion criterion was lack of a parallel study design.Our primary endpoint was all-cause mortality. A secondary endpoint was the mean difference (MD) in LVEF during the follow-up. Endpoints were assessed through meta-analyses computing hazard ratios (HRs) and MDs. Mantel-Haenszel and DerSimonian random effect models were applied, respectively. LVEF&lt;41% was used as a surrogate for HF in a sensitivity analysis. Results: Overall,1738 studies were found from the data searches. Of these, 24 fulfilled the inclusion criteria (HF, N=15). The range of age was 60-75 years and 14 to 74% were women. The follow-up time varied between 3 to 96 months. AVJA as compared with pharmacological therapy reduced all-cause mortality by 27% in patients with AF (Fig. 1), whereas the LVEF MD between groups was not significantly different (Fig. 2). In HF patients, mortality was significantly favouring AVJA as compared with pharmacological therapy (HR, 0.68; 95% confidence interval [CI], 0.51 to 0.91; P=0.009) but not for the LVEF (MD, 1.12; 95% CI, -2.90 to 5.14; P=0.54). In patients without HF, neither mortality nor the LVEF MD were significantly different between AJVA and pharmacological therapy (results not reported). Conclusion: Mortality was significantly reduced in the AVJA group as compared with the pharmacological therapy group. This benefit was only persistent in HF patients in a sensitivity analysis.
Abstract 10402: Activated Protein C Rescues Sepsis-Associated Cardiac Dysfunction and Renal Injury in Aging
Authors: Meredith Krause-Hauch, Di Ren, Lily Slotabec, Hao Wang, Kayla Davitt, Zehui Li, Linda Ines Zoungrana, Ji Li
Journal: Circulation (2022)

Introduction: Sepsis is a progressive life-threatening condition in which mortality has been consistently linked to increasing organ dysfunction. We have found that activated protein C (APC) has cytoprotective and anti-inflammatory properties in cardiovascular disease. Whether APC is critical for maintaining systemic homeostasis under sepsis in aging remains unknown. Hypothesis: Administration of recombinant APC ameliorates sepsis-associated renal injury and cardiac dysfunction in aging via EPCR (endothelial cell protein C receptor). Methods: Young (3-6 months) and aged (18-21 months) C57BL/6J wild type (WT), and EPCR point mutation (EPCR R84A/R84A ) knock in C57BL/6J mice were subjected to cecal ligation and puncture (CLP) surgery. APC (0.2 μg/g) was injected (i.p.) 1 hour after CLP surgery and every 24 hours to determine the therapeutic effects of APC on CLP-induced sepsis. Cardiac function was assessed daily via echocardiogram. Results: The Kaplan-Meier survival curve showed that the survival rate of young mice is 90% and of aged mice is 0% on day 7 of post-CLP. Moreover, the spleens were significantly enlarged in both young and aged CLP WT mice. Intriguingly, administration of recombinant APC can keep all young animals' survival and increased survival rate of aged animals to 65% on day 7 of post-CLP. The spleen size of young/aged CLP groups were significantly reduced by APC treatment. However, the beneficial effects of APC on the survival rate and spleen enlargement caused by CLP were abolished in EPCR R84A/R84A mice versus EPCR WT/WT littermates. The renal tubules necrosis score and cardiac dysfunctions caused by CLP were worse in aged versus young mice, but APC treatment significantly rescued CLP-caused renal pathology and cardiac dysfunctions of young/aged mice and the rescuing capacity of APC for both renal pathology and cardiac dysfunctions in aged versus young mice was stronger. In addition, APC treatment reduced circulating inflammatory monocytes and neutrophils during CLP-induced sepsis in young/aged WT but not EPCR R84A/R84A mice Conclusions: Sepsis associated mortality is increased in aging. APC treatment can ameliorate age-related sepsis renal injury and cardiac dysfunctions through receptor EPCR to reduce sepsis related mortality.
Abstract 10548: Atrial Fibrillation Worsens Sports Performance in Athletes; Greatest Improvement Seen With Ablation: A Stopafib.org Survey
Authors: Ali K Khan, Hyon Jae Lee, Mellanie T Hills, Melissa Moss, Brenna Lara, Raymond Baumann, Cynthia Brandt, Rachel J Lampert
Journal: Circulation (2022)

Introduction: Anecdotally, both atrial fibrillation (AF) and medications for AF, are poorly tolerated in athletes. However, data are lacking. Methods: An internet-based survey, initiated via StopAfib.org, queried the impact of AF and treatment modalities on sports performance, training, and well-being. Performance, (rated in comparison to personal best), frequency of training and competition were categorized ordinally and compared prior to onset of AF symptoms versus when symptoms at worst, via paired Wilcoxon, and then compared in relation to participants’ AF treatments. Results: Between 5/13/19 and 2/29/20, 802 athletes responded, including 78% males, 22% female, median age 61 to 70 years . The most reported sports were cycling (25%) and running (20%). Median time since diagnosis was 3 to 5 years. When participants’ symptomatology was at worst, the median frequency was at least once a week, most commonly palpitations, fatigue, and decreased exercise tolerance. Development of AF was associated with declining sports performance, competition, and training frequency as shown in the table below. Of 471 participants who decreased their exercise regimen, 31% reported no change in symptoms, 56% reported a decreased frequency of AF, and 13% reported no further AF. Among athletes that received treatment, ablation was associated with the greatest improvement in sports performance compared with ablation plus medications or medications alone (see table below). Of 262 athletes currently on medication, 27% reported that it was completely effective, 58% partially effective, and 15% not effective. Of 653 athletes that have taken medication currently and/or in the past, 43% reported side effects, most commonly fatigue, low energy, or decreased athletic performance. Conclusions: In athletes, AF was associated with decline in sports performance. Among AF treatment modalities, ablation was associated with the greatest improvement in sports performance.
Abstract 10048: Effect of Transitioning From Conventional Cardiac Troponin to High Sensitivity Cardiac Troponin on Hospital Resources- A Single Center Experience
Authors: Mina M Kerolos, Jian Chu, Eliseo Vazquez, Akilesh Honasoge, Yanina A Purim-Shem-Tov, elif yucebay, Steve Attanasio
Journal: Circulation (2022)

Introduction: In comparison to conventional cardiac troponin (cTn), high sensitivity cardiac troponin (hs-cTn) assay is associated with improved detection of myocardial infarction (MI). From literature review, resource utilization seems variable across institutions. This study sought to determine the effect of converting to hs-cTn on hospital resources. Hypothesis: hs-cTn is associated with overall decrease in resource utilization Methods: We performed a descriptive retrospective analysis of resource utilization at Rush University Medical Center (Chicago, IL) over the period of transition (July 6, 2021) from a cTn to hs-cTn assay using data extracted from the electronic health record. Inclusion criteria included Emergency Department (ED) encounters between January 1, 2021 and December 31, 2021 with chief complaints of “chest pain” or “dyspnea” with an associated troponin order. The primary endpoints were percentage of ED discharges. Secondary endpoints included the number of cardiac studies ordered including troponins, electrocardiograms (ECG), echocardiograms, stress tests, and coronary angiograms. Univariable comparisons of these endpoints were performed using Student’s t-test for continuous variables and Chi-square tests for binary/categorical variables. Results: A total of 5113 encounters were analyzed. hs-cTn was associated with an overall increased ED discharge in patients with negative troponin tests (44.1% vs. 29.9%, P&lt;0.01). In terms of cardiac testing per encounter, hs-cTn compared to cTn was associated with a marginal increase in number of troponin tests (1.9 vs. 1.6, P&lt;0.01), electrocardiograms (3.0 vs. 2.9, P=0.01), Echocardiograms (0.5 vs. 0.4, P&lt;0.01). There was a decrease in the utilization of stress testing (0.21 vs 0.26, P&lt;0.01). There was a trend towards increased coronary angiography per encounter (0.11 vs. 0.09, P=0.05) and an increase in total coronary angiography use during the hs-cTn period compared to cTn (227//2471 (9.2%) vs. 195/2642 (7.4%, P=0.02)) Conclusion: Transitioning from cTn to hs-cTn was associated with increased ED discharges, marginal increase in troponin tests, ECGs, echocardiograms. There was a decrease in stress testing but increase in total coronary angiography.